| ||Principal Investigators
|Francis McMahon, M.D.
||Dr. McMahon graduated
University of Pennsylvania in 1982, where he majored in Biology. After a year in Europe as a Rotary Scholar,
he enrolled in The Johns Hopkins University School of Medicine, where he received his M.D. in 1987. He stayed
on at Hopkins to complete a medical internship, a residency in adult psychiatry and a post-doctoral fellowship
in psychiatric genetics before joining the faculty in 1993. In 1998, he became Associate Professor of Psychiatry
at the University of Chicago, where he also served as medical director of the Electroconvulsive Therapy clinic.
In 2002, he came to the National Institute of Mental Health to establish a new
Genetics Unit within the Intramural Research Program. Dr. McMahon is the recipient of several
honors and awards. Most recently he was named the 30th Mallinckrodt Scholar by the Edward F. Mallinckrodt
Foundation. He serves as a scientific advisor for the National Tourette Syndrome Association, the University of
Antwerp, the RIKEN Brain Science Institute, and the National Institutes of Health Center for Scientific Review,
as well as numerous scientific journals.
|Our mission is to identify the genes that contribute to the risk for mood and anxiety disorders so that better methods of diagnosis and treatment can be developed.
Mood and anxiety disorders reflect a complex genetic architecture ranging from common alleles conferring modest risk for what may prove to be a broad range of psychopathology, to alleles that help shape the clinical picture of disease and response to treatment. Rarer alleles may also exist that confer larger risk in a fraction of individuals and families. If even a few of these alleles can be firmly identified, new windows into the pathobiology of common psychiatric disorders may be opened, enabling the development of new methods of diagnosis and treatment.
Right now this is discovery science, requiring a broad range of approaches that survey genetic variation across the genome in order to generate hypotheses that can be tested by replication, and then subjected to functional analysis.
We are currently pursuing three complementary discovery strategies:
1) Genetic studies to identify alleles that contribute to bipolar affective disorder (BPAD), using a combination of association, linkage, copy number and sequencing methods. Our studies are informed by our long-term effort to produce a large database of BPAD phenotypes and identify familial component phenotypes with increased genetic homogeneity. This work complements large-scale genome-wide association studies, including the Genetic Association Information Network (GAIN), of which we are a part.
2) Pharmacogenetic studies aimed at the identification of markers that predict anti-depressant response and adverse events in patients with major depressive disorder. These studies offer an alternative approach to gene finding that has several advantages over case-control studies of disease, and may ultimately aid the development of more personalized treatment approaches.
3) Genetic association studies of neuroimaging phenotypes that are candidate endophenotypes for mood and anxiety disorders. Endophenotypes offer a powerful, biologically relevant strategy for mapping risk alleles. We collaborate with several neuroimaging groups to study the genetic architecture of traits measured by positron emission tomography (PET), as well as structural and functional magnetic resonance imaging (MRI).
|Representative Selected Recent Publications:
- Schulze TG, Detera-Wadleigh SD, Akula N, Gupta A, Kassem L, Steele J, Pearl J, Strohmaier J, Breuer R, Schwarz M, Propping P, Nöthen MM, Cichon S, Schumacher J; NIMH Genetics Initiative Bipolar Disorder Consortium, Rietschel M, McMahon FJ. Two variants in Ankyrin 3 (ANK3) are independent genetic risk factors for bipolar disorder. Mol Psychiatry. 14:487-91. 2009. [pdf]
- Cabanero M, Laje G, Detera-Wadleigh S, McMahon FJ. Association study of phosphodiesterase genes in the Sequenced Treatment Alternatives to Relieve Depression sample. Pharmacogenet Genomics. 19:235-8. 2009. [pdf]
- Perlis RH, Laje G, Smoller JW, Fava M, Rush AJ, McMahon FJ. Genetic and clinical predictors of sexual dysfunction in citalopram-treated depressed patients. Neuropsychopharmacology. 34:1819-28. 2009. [pdf]
- Baum AE, Akula N, Cabanero M, Cardona I, Corona W, Klemens B, Schulze TG, Cichon S, Rietschel M, Nothen MM, Georgi A, Schumacher J, Schwarz M, Abou Jamra R, Hofels S, Propping P, Satagopan J, Detera-Wadleigh SD, Hardy J, NIMH Genetics Initiative Bipolar Disorder Consortium, and McMahon FJ. A genome-wide association study implicates diacylglycerol kinase eta (DGKH) and several other genes in the etiology of bipolar disorder. Mol Psychiatry. 13:197-207. 2008. [pdf]
- Laje G, Paddock S, Manji H, Rush AJ, Wilson AF, Charney D, and McMahon FJ. Genetic markers of suicidal ideation emerging during citalopram treatment of major depression. Am J Psychiatry. 164:1530-8. 2007. [pdf]
- Paddock S, Laje G, Charney D, Rush AJ, Wilson AF, Sorant AJ, Lipsky R, Wisniewski SR, Manji H, and McMahon FJ. Association of GRIK4 with outcome of antidepressant treatment in the STAR*D cohort. Am J Psychiatry. 164:1181-8. 2007. [pdf]
||Chief, Genetic Basis of Mood and Anxiety Disorders
National Institute of Mental Health
NATIONAL INSTITUTES OF HEALTH
Bldg. 35, Rm 1A202
35 Convent Drive MSC 3719
Bethesda, MD 20892-3719
|Email Dr. McMahon
|Lab Web Site: